Hashmi Atif Ali, Brogi Edi, Wen Hannah Y
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Diagn Pathol. 2025 Mar 1;20(1):26. doi: 10.1186/s13000-025-01623-4.
Breast cancer, especially triple-negative breast cancer (TNBC), lacks sensitive and specific diagnostic markers that can reliably differentiate it from carcinomas of other origins. TRPS1 is a relatively new immunohistochemical (IHC) marker that has demonstrated higher sensitivity in breast cancer, including TNBC. However, with the increasing use of this marker, broader immunoreactivity has been observed. This study aims to evaluate the utility of TRPS1 for establishing carcinoma of mammary origin. We compared the diagnostic sensitivity and specificity of TRPS1 with that of other IHC markers (GATA3 and SOX10).
In this retrospective study, we reviewed TRPS1 IHC performed at our center between 07/2022 and 06/2024, to evaluate the expression of TRPS1 in breast carcinoma (primary and distant metastasis) and in other malignancies. The sensitivity and specificity of TRPS1 in determining carcinoma of breast origin were compared with those of GATA3 and SOX10.
The study cohort comprised 106 cases, including 17 cases at the primary site, and 89 samples of distant metastasis. After correlation with morphology, immunophenotype and molecular studies, 94 cases (88.7%) were characterized as breast primary (37.9% ER+/HER2neu-, 4.6% ER-/HER2neu+, 1.1% ER+/HER2neu+, 56.3% TNBC), whereas 12 (11.3%) were non-breast primary. The non-breast primary sites included lung, bladder, Mullerian, and gastrointestinal. The sensitivity and specificity of TRPS1 were 93.6% and 58.3%, respectively. Conversely, GATA3 demonstrated a sensitivity and specificity of 76.9% and 66.7%, respectively. SOX10 exhibited the lowest sensitivity at 47.9%, but with the highest specificity at 100%. There were three cases of metastatic breast carcinoma (sites: bladder, lung, and bone), where TRPS1 was the only positive marker, whereas GATA3 and SOX10 were negative. TRPS1 showed a higher positivity rate (92.0%) in TNBC compared to GATA3 (63.4%) and SOX10 (56.7%). TRPS1 expression was also observed in other tumor types, including carcinoma of Mullerian origin, bladder, and lung, limiting its utility in the differential diagnosis.
Our study demonstrated a higher sensitivity of TRPS1 expression in establishing carcinoma of breast origin compared with GATA3 and SOX10, consistent with previous reported studies. However, the specificity of TRPS1 was lower than that of GATA3 and SOX10. These findings suggest that while TRPS1 can be used as a reliable marker for breast cancer, its expression in other tumor types should be carefully interpreted to avoid diagnostic pitfalls.
乳腺癌，尤其是三阴性乳腺癌（TNBC），缺乏能够可靠地将其与其他来源的癌区分开来的敏感且特异的诊断标志物。TRPS1是一种相对较新的免疫组织化学（IHC）标志物，已在包括TNBC在内的乳腺癌中显示出更高的敏感性。然而，随着该标志物使用的增加，观察到其免疫反应性更广泛。本研究旨在评估TRPS1在确定乳腺来源癌方面的效用。我们比较了TRPS1与其他IHC标志物（GATA3和SOX10）的诊断敏感性和特异性。
在这项回顾性研究中，我们回顾了2022年7月至2024年6月在我们中心进行的TRPS1 IHC检测，以评估TRPS1在乳腺癌（原发性和远处转移）及其他恶性肿瘤中的表达。将TRPS1在确定乳腺来源癌方面的敏感性和特异性与GATA3和SOX10的进行比较。
研究队列包括106例病例，其中原发性部位17例，远处转移样本89例。经与形态学、免疫表型和分子研究相关分析后，94例（88.7%）被鉴定为乳腺原发性癌（37.9%雌激素受体阳性/人表皮生长因子受体2阴性，4.6%雌激素受体阴性/人表皮生长因子受体2阳性，1.1%雌激素受体阳性/人表皮生长因子受体2阳性，56.3%三阴性乳腺癌），而12例（11.3%）为非乳腺原发性癌。非乳腺原发性部位包括肺、膀胱、苗勒管和胃肠道。TRPS1的敏感性和特异性分别为93.6%和58.3%。相反，GATA3的敏感性和特异性分别为76.9%和66.7%。SOX10的敏感性最低，为47.9%，但特异性最高，为100%。有3例转移性乳腺癌（部位：膀胱、肺和骨），其中TRPS1是唯一阳性标志物，而GATA3和SOX10为阴性。与GATA3（63.4%）和SOX10（56.7%）相比，TRPS1在三阴性乳腺癌中的阳性率更高（92.0%）。在其他肿瘤类型中也观察到TRPS1表达，包括苗勒管来源癌、膀胱癌和肺癌，这限制了其在鉴别诊断中的效用。
我们的研究表明，与GATA3和SOX10相比，TRPS1表达在确定乳腺来源癌方面具有更高的敏感性，这与先前报道的研究一致。然而，TRPS1的特异性低于GATA3和SOX10。这些发现表明，虽然TRPS1可作为乳腺癌的可靠标志物，但应仔细解读其在其他肿瘤类型中的表达，以避免诊断陷阱。
